Effects of Intermittent Hypoxia Training With Iron Supplementation on Red Blood Cells and Iron Levels in Trained Athletes (IHIT-IRON)

SHORT-TERM INTERMITTENT HYPOXIA TRAINING INDUCES POSITIVE ERYTHROPOIETIC ADAPTATIONS BUT DECREASING DRASTICALLY IRON RESERVES

This study investigates how training under conditions of reduced oxygen (intermittent hypoxia) affects the body's ability to produce red blood cells and manage iron levels, compared to training under normal oxygen conditions. Red blood cells are essential for transporting oxygen throughout the body, and their production depends on having enough available iron.

Thirty-two physically trained participants completed a 3-week training program, either in low-oxygen conditions or in normal oxygen conditions. All participants followed the same diet and received daily supplements of iron and vitamins to ensure adequate nutritional support.

The main hypothesis of this study is that training in low-oxygen conditions stimulates the production of red blood cells more strongly than training in normal oxygen conditions, and that this increased production requires the body to use stored iron, potentially lowering iron reserves.

Results showed that participants training in low-oxygen conditions experienced a greater increase in red blood cells and related markers compared to those training in normal conditions. At the same time, their stored iron levels decreased, suggesting that the body was using its iron reserves to support the increased production of red blood cells. In contrast, participants training in normal oxygen conditions showed smaller changes and maintained or slightly increased their iron stores.

These findings suggest that low-oxygen training can enhance the body's capacity to produce red blood cells but may also reduce iron reserves. This highlights the importance of monitoring iron levels during such training programs, especially in athletes or individuals with conditions related to low oxygen availability, such as anemia.

Overall, this study aims to improve understanding of how oxygen availability influences blood health and may help guide future strategies that combine hypoxia training and iron supplementation to support performance and treat certain medical conditions.

Study Overview

• Status: Completed
• Conditions: Hypoxia; Iron Metabolism Disorders; Erythropoiesis
• Intervention / Treatment: Other: Control group (CG); Other: Hypoxia group (HG): trained at simulated altitudes between 4,450 and 5,850 m

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Alicante
    • Elche, Alicante, Spain, 03202
      • University Miguel Hernández of Elche

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male sex
• Adult age (≥18 years)
• Federated mountain sports practitioner (alpinist, trail runner, ski mountaineer, or endurance runner)
• Normal hemoglobin levels at screening (≥13 g/dL)
• Residence at elevations below 700 m
• Provision of written informed consent prior to enrollment
• Agreement to comply with the principles of the Declaration of Helsinki (WMA, 2024 revision)

Exclusion Criteria:

• Stay at altitudes above 2,000 m within the previous 2 months prior to enrollment
• Any form of anemia at screening (hemoglobin <12-13 g/dL)
• Sports-related pseudoanemia
• Presence of cardiovascular or respiratory pathologies, as determined by the medically supervised VO₂max exercise test
• Female sex

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group (CG); Trained at sea-level conditions	Other: Control group (CG); 3-week normoxic training program (14 sessions, 90 min/session) with identical exercise structure to the hypoxia group (strength-resistance circuit + cycling intervals), performed at sea-level oxygen conditions inside the same tent to ensure blinding. Frequency: 4-5 sessions/week. All participants received daily oral supplementation: iron 60 mg (ferrous sulfate + ferrous fumarate) + vitamin C 200 mg + folic acid 200 µg + vitamin B12 6 µg. Diet provided ~55 kcal/kg/day (carbohydrates 7-8 g/kg, protein 1.6-2 g/kg, fat 1-1.5 g/kg).
Experimental: Hypoxia group (HG); Trained at simulated altitudes between 4,450 and 5,850 m	Other: Hypoxia group (HG): trained at simulated altitudes between 4,450 and 5,850 m; 3-week normobaric intermittent hypoxia training program (14 sessions, 90 min/session: 60 min active + 30 min passive hypoxia) at simulated altitudes of 4,450-5,850 m (SaO₂ ~80%). Training combined strength-resistance circuit (30 min) and high-intensity cycling intervals (30 min). Frequency: 4-5 sessions/week. All participants received daily oral supplementation: iron 60 mg (ferrous sulfate + ferrous fumarate) + vitamin C 200 mg + folic acid 200 µg + vitamin B12 6 µg. Diet provided ~55 kcal/kg/day (carbohydrates 7-8 g/kg, protein 1.6-2 g/kg, fat 1-1.5 g/kg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin concentration	Venous blood hemoglobin concentration (g/dL) measured at baseline and 3 days after completion of the 3-week intervention. Blood samples collected in the morning (08:00-10:00 h) after overnight fast (≥8 h) and 10 min of seated rest, analyzed by automated laboratory analyzer following CLSI standards.	Baseline and 3 weeks (end of intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Red blood cell count	Venous blood erythrocyte concentration (×10⁶ cells/mm³) measured at baseline and 3 days after completion of the 3-week intervention. Blood samples collected in the morning (08:00-10:00 h) after overnight fast (≥8 h) and 10 min of seated rest, analyzed by automated laboratory analyzer following CLSI standards.	Baseline and 3 weeks (end of intervention)
Hematocrit	Percentage of red blood cells in total blood volume (%) measured at baseline and 3 days after completion of the 3-week intervention. Blood samples collected under identical conditions to primary outcome measure.	Baseline and 3 weeks (end of intervention)
Serum ferritin	Serum ferritin concentration (ng/mL) as an indicator of iron storage status, measured at baseline and 3 days after completion of the 3-week intervention. Obtained from serum separator tubes analyzed by automated laboratory analyzer following CLSI standards.	Baseline and 3 weeks (end of intervention)
Reticulocyte count	Percentage of reticulocytes (immature red blood cells) in peripheral blood (%), used as an indirect indicator of erythropoietic activity. Measured at baseline and 3 days after completion of the 3-week intervention under identical sampling conditions.	Baseline and 3 weeks (end of intervention)

Collaborators and Investigators

• Sponsor: Néstor Vicente-Salar
• Investigators: Study Director: Enrique Roche, Full Professor, University Miguel Hernández of Elche

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2011
• Primary Completion (Actual): June 30, 2014
• Study Completion (Actual): July 15, 2014

Study Registration Dates

• First Submitted: July 17, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Signs and Symptoms, Respiratory; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Hypoxia; Iron Metabolism Disorders; Investigative Techniques; Epidemiologic Research Design; Epidemiologic Methods; Research Design; Methods; Control Groups
• Other Study ID Numbers: PS09/01093

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No